Search PubMed⌕ Search

Biomedical subjects

C A Ryan

Publications and source records attributed to C A Ryan.

At least 181 records · Page 10Linked to original sources
PubMed1989

A predictive mouse ear-swelling model for investigating topical phototoxicity.

Predictive models should be used to determine the phototoxic potential of consumer products intended for topical exposure and outdoor use. To determine the potential of a compound to elicit a phototoxic reaction, a mouse ear-swelling model, which uses a xenon arc ultraviolet (UV) solar simulator as the radiation source, was used. The UV solar simulator delivered UV radiation from 290 to 400 nm (UVB + UVA) or from 320 to 400 nm (UVA) when appropriate filters were used. With this model, the phototoxic potential of nine known phototoxins and three negative test materials was successfully demonstrated. Based on the time of onset of the phototoxic response following test material application and irradiation, both immediate (20-30 min) and delayed-type (48-96 hr) phototoxic responses were demonstrated using this model with anthracene and 8-methoxypsoralen, respectively. The optimal time for irradiation after application of 8-methoxypsoralen to the ears was 30-60 min. Irradiation of ears immediately after treatment with 8-methoxypsoralen or 6 hr after application resulted in little or no phototoxic response. The phototoxic response to 8-methoxypsoralen was dependent upon the UVA dose and, when tested at a constant UVA dose, the response was concentration dependent. To obtain an optimal phototoxic response to 7-methoxycoumarin, both UVB and UVA radiation were required. These results show that the mouse ear-swelling model, which is quantifiable and more objective than models based on subjective evaluation of skin changes, is an excellent model for investigative and predictive phototoxicity testing.

Administration, Cutaneous↗
PubMed1989

In vitro phosphorylation of plant plasma membrane proteins in response to the proteinase inhibitor inducing factor.

A polygalacturonide purified from a tomato leaf pectic polysaccharide that induces the systemic synthesis of proteinase inhibitors in tomato plants enhances the phosphorylation of specific proteins in plasma membrane fractions isolated from tomato and potato leaves. In tomato plasma membranes, two proteins of 34 and 29 kDa show enhanced phosphorylation in response to the polyuronide. In potato plasma membranes, only a protein of 34 kDa exhibited enhanced phosphorylation due to the polyuronide. A noncarbohydrate class of proteinase inhibitor inducing factor, recently identified by workers in this laboratory, resulted in the in vitro hyperphosphorylation of a family of proteins of approximately 27 kDa. The phosphorylation of specific polypeptides in leaves in response to the same factors that induce the expression of proteinase inhibitor genes suggests that protein kinases may play an important role in the mechanism of signal transduction leading to defense gene expression.

Journal Article↗
PubMed1989

Inhibition of radiation-induced transformation of C3H/10T1/2 cells by carboxypeptidase inhibitor 1 and inhibitor II from potatoes.

In the current study, the ability of four protease inhibitors to suppress radiation-induced transformation of C3H/10T1/2 cells was investigated. The inhibitors tested included: (i) aprotinin (a serine protease inhibitor), (ii) N-acetyl-L-tyrosine ethyl ester (a chymotrypsin substrate and competitive inhibitor of protein degradation), (iii) carboxypeptidase inhibitor (a metallo-exopeptidase inhibitor) and (iv) Inhibitor II (a chymotrypsin/trypsin inhibitor). While none of the inhibitors were toxic to the cells at the concentrations employed, only carboxypeptidase inhibitor and inhibitor II are internalized radiation-induced transformation in a statistically significant manner. Utilizing fluorescent labeled inhibitors, we found that carboxypeptidase inhibitors and Inhibitor II are internalized by the cells. Fluorescent-labeled inhibitor could be observed in the cells within 15 min of incubation and is present in distinct intercellular vacuoles within 1 h. These results indicate that carboxypeptidase inhibitor and Inhibitor II are internalized by C3H/10T1/2 cells and thus would be able to inhibit intracellular proteases (or other enzymes) involved in the conversion of a cell to the malignant state.

Animals↗
PubMed1989

Relationship between core/peripheral temperature gradient and central hemodynamics in children after open heart surgery.

Anterior thigh, pretibial and midfoot surface temperatures (MFT) were measured by an infrared thermometer in 17 children after open heart surgery. Core temperature was measured by pulmonary artery thermistor and cardiac index (CI) by thermodilution. No significant relationship existed between the previous hour's urinary output (ml/m2.h) and either systemic vascular resistance index (SVRI) and CI. MFT was inversely related to SVRI (r = -5.3; p less than .0001) but not to CI. The core/peripheral temperature gradient correlated directly with SVRI (r = .38, p less than .01) and inversely with CI (r = -.28, p less than .05). There was no improvement in any of the correlation coefficients when hemodynamic variables were tested against temperature gradients from core to thigh and thigh to foot. Although these relationships are statistically significant, we conclude that they are not strong enough to be of value in predicting central hemodynamic status in children after heart surgery.

Body Temperature↗
PubMed1989

Hemodynamic responses to PaCO2 in children after open heart surgery.

We studied the hemodynamic effects of acute alterations in PaCO2 in ten ventilator-dependent children after open heart surgery. Despite end-tidal CO2 monitoring, five children inadvertently developed PaCO2 greater than 50 torr during the study. Increasing and decreasing PaCO2 in these children resulted in significant parallel changes in cardiac index (CI), oxygen delivery, physiologic shunt, mean pulmonary pressure, and right ventricular stroke work index, and inverse changes in systemic vascular resistance index (p less than .01). No significant hemodynamic changes were observed with alterations in PaCO2 in children whose PaCO2 remained less than 50 torr. These findings are partly related to significantly larger reductions in PaCO2 which occurred in the hypercarbic children compared to the others (25 vs. 12 torr; p less than .001). Heart rate, mean arterial BP, and venous filling pressures did not change significantly in either group. We conclude that mean alterations in PaCO2 less than or equal to 12 torr (range 28 to 50) have no significant effect on CI in children after open heart surgery. However, moderate hypercarbia and its correction to a mean PaCO2 of 30 torr are associated with significant effects on central hemodynamics. Moreover, no significant changes in the commonly monitored physiologic variables were observed despite large variations in PaCO2.

Carbon Dioxide↗
PubMed1989

Functional analysis of the 3' control region of the potato wound-inducible proteinase inhibitor II gene.

Proteinase inhibitor genes are expressed strongly in specific plant tissues under both developmental and environmental regulation. We have studied the role of the 3' control region of the potato proteinase inhibitor II gene (PI-II) that is inducible in leaves in response to herbivore attacks or other severe wounding. Comparison of the terminator from the PI-II gene with two different terminators from the 6b and 7 genes, driven by a common PI-II promoter-cat fusion molecule, indicated that the PI-II terminator provided the most efficient expression of cat. The PI-II terminator also caused a significantly elevated cat gene expression driven by the cauliflower mosaic virus 35S promoter. The increase in the level of expression is probably not due to the presence of an enhancer element in the PI-II terminator region, but to cis-acting elements involved in mRNA processing or stability. Both transient and stable transformation analyses of the deletion mutants in the 3'-flanking sequence indicated that about a 100-base pair DNA fragment surrounding the polyadenylation site is essential for the efficient gene expression. This region seems to consist of several regulatory elements, including the conserved sequence, CGTGTCTT, which is located 9 bases downstream from the polyadenylation site. The elements appear to contribute to the increased stability of mRNAs containing the PI-II terminator.

Amino Acid Sequence↗
PubMed1989

Contact photoallergy testing of sunscreens in guinea pigs.

The potential of 3 sunscreens (p-aminobenzoic acid, 4-isopropyldibenzoylmethane and homosalate) and 2 known human photoallergens (musk ambrette and tetrachlorosalicylanilide) to cause photoallergy, phototoxicity, and/or contact sensitization was determined using a guinea pig photoallergy model, as previously described by Harber and associates. The model was slightly modified by employing 6 exposures over 2 weeks and using Hill Top Chambers for application of the test material. Contact photoallergy was detected in guinea pigs treated with musk ambrette or tetrachlorosalicylanilide (TCSA), although with TCSA, a lower incidence of contact sensitivity and phototoxicity was also detected. The results of studies conducted with sunscreens showed that p-aminobenzoic acid was photoallergenic, whereas homosalate and 4-isopropyl-dibenzoylmethane (Eusolex 8020) were not. However, contact sensitization, and to a lesser degree primary irritation, was detected with Eusolex 8020 at the concentrations employed in this study. The results of these studies suggest that this guinea pig model is a suitable model for assessing the photoallergic potential of various compounds, including the sunscreens tested in this study.

4-Aminobenzoic Acid↗
PubMed1989

Prostacyclin and pathogenesis of hemodynamic abnormalities of diabetic ketoacidosis in rats.

The pathogenesis of the hemodynamic abnormalities of diabetic ketoacidosis (DKA) is not well understood. Previous studies suggest that prostacyclin (PGI2) production by adipose tissue is increased in DKA. We investigated the role of PGI2 in the pathogenesis of the reduced vascular resistance in DKA. Rats with streptozocin-induced DKA were anesthetized with pentobarbital sodium, and flow was measured with an electromagnetic probe on the infradiaphragmatic aorta. The plasma level of 6-keto-PGF1 alpha (stable derivative of PGI2) was higher (mean +/- SE 0.91 +/- 0.05 ng/ml) and vascular resistance lower (4.9 +/- 0.2 mmHg.ml-1.min-1.100 g-1 [resistance units, RU]) in 67 rats with DKA than in 21 normal rats (0.34 +/- 0.03 ng/ml, P less than .01, and 9.0 +/- 0.7 RU, P less than .01, respectively). Inhibition of cyclooxygenase activity with either indomethacin or meclofenamic acid reduced the plasma 6-keto-PGF1 alpha level but failed to raise vascular resistance. Infusions of PGI2 in rats with DKA demonstrated that the vasculature was responsive to PGI2. Inhibition of cyclooxygenase activity not only reduced PGI2 production but also suppressed renin release. When the effects of the renin-angiotensin system were excluded by bilateral nephrectomy, indomethacin caused a significant increase (P less than .05) in vascular resistance. Thus, the failure of cyclooxygenase inhibitors to raise vascular resistance in DKA was a result of concurrent suppression of vasodilator (PGI2) and vasoconstrictor (renin-angiotensin system) mechanisms that are activated in DKA. Insulin administration increased vascular resistance (P less than .01) and decreased the level of plasma 6-keto-PGF1 alpha (P less than .01). Combined administration of PGI2 and insulin did not alter vascular resistance, suggesting that the increase in vascular resistance with insulin was predominantly due to the reduction of circulating PGI2. Thus, vascular resistance is decreased in DKA primarily as a result of the vasodilator effects of PGI2 produced by adipose tissue. The activation of the renin-angiotensin system represents a partial compensation. The increase in PGI2 production may contribute to the hypotension and mortality of DKA.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Discordance of signs in monozygotic twins concordant for the Goldenhar anomaly.

Concordance for Goldenhar anomaly has been described in monozygotic (MZ) twins on 2 occasions but never in dizygotic (DZ) twins. In both cases the twins were similarly, although not identically, affected. We report on a pair of probably monozygotic twins (8% probability of DZ) who presented with extremely diverse manifestations of this anomaly complex. One of them required a tracheostomy because of obstructive apnea due to severe micrognathia and subsequently died. This twin had a midline lower lip cleft which has not previously been described in the Goldenhar anomaly.

Diseases in Twins↗
PubMed1988

Risk factors for fatal diarrhea: a case-control study of African children.

Few studies have determined risk factors for diarrheal deaths in developing areas. The Ministry of Health of Lesotho, southern Africa, reported that 9.5% of children under five years of age who were hospitalized for diarrhea in 1984 died. Of 104 children under five years of age who died during hospitalization for diarrhea, 85% were aged 24 months or younger and had nonbloody diarrhea during the warm season. We conducted two retrospective case-control studies of children aged 24 months or younger admitted for diarrhea at two hospitals in 1983 and 1984, comparing 44 who died with 89 who survived. Eight factors were significantly associated (p less than 0.05) with death at one or both hospitals by univariate analysis: diagnosis of a major infection, age under six months, illness for seven days or more before admission, thrush or stomatitis on admission, severe dehydration, history of vomiting, dehydration that had not improved after 12 hours in the hospital, and fever or subnormal temperature. Multivariate analysis of data from one hospital showed the first three factors to be significantly associated with death. Cases and controls were similar in sex and in degree of malnutrition. This study identified children at high risk for death from diarrhea.

Child, Preschool↗
PubMed1988

Evaluation of pulse oximetry as a continuous monitoring technique in the neonatal intensive care unit.

We tested a number of pulse oximeters in a neonatal ICU to assess their performance as continuous monitors. Using a computer-based data acquisition system and a movement sensor, we determined the proportion of time that the oximeter was unreliable as the duration of monitored time that the oximeter heart rate (HR) differed from a "true" HR by greater than 10 beat/min using each of the oximeters in both their short and long averaging mode. The tested devices were found to be unreliable for 11.9% to 25% in the short averaging mode, and from 13.8% to 29% in the longer averaging mode. Most of the HR discrepancy was secondary to movement of the extremity. A newer model of one of the devices, which uses ECG R-wave detection to trigger optical pulse scanning, was associated with markedly reduced motion artifact (2.1% to 4.1%) when it accurately interpreted HR. The response of the devices to an acute loss of pulsation revealed differences in design and performance with some oximeters indicating zero saturation and others continuing to display a value while indicating a "low quality signal." Pulse oximeters are a valuable adjunct to clinical oxygen monitoring and, when properly applied and reliably indicating the infant's HR, will accurately reflect arterial saturation (r = .8, p less than .0001). ECG synchronization appears to reduce motion artifact when the ECG R-wave is detected.

Chronic Disease↗
PubMed1988

Home nebulizers in childhood asthma. Parental perceptions and practices.

Seventy five percent of 91 parents of asthmatic children (aged 6 months to 15.4 years) with home nebulizers, responded to a questionnaire that sought to document parental experience with this form of therapy. The most common indications for acquiring a nebulizer were inability to use metered dose inhalers and poor response or intolerance to oral medications. When the children were classified into those who used the nebulizer daily (27/69) and those who used it less than daily (42/69), we found that the daily users were more likely to be in the severest category of asthma, by parental assessment, prior to the home nebulization program (p = 0.0035). Retrospective, uncontrolled comparison before and after the acquisition of a home nebulizer showed significant decreases both in hospital admissions (1.7 vs 0.7; p less than 0.001) and total in-patient days (4.1 vs 1.7; p less than 0.0001). Home nebulizers are well tolerated by parents and children alike and may be associated with decreased morbidity.

Adolescent↗
PubMed1987

Massive outbreak of antimicrobial-resistant salmonellosis traced to pasteurized milk.

Two waves of antimicrobial-resistant Salmonella typhimurium infections in Illinois totaling over 16 000 culture-confirmed cases were traced to two brands of pasteurized 2% milk produced by a single dairy plant. Salmonellosis was associated with taking antimicrobials before onset of illness. Two surveys to determine the number of persons who were actually affected yielded estimates of 168 791 and 197 581 persons, making this the largest outbreak of salmonellosis ever identified in the United States. The epidemic strain was easily identified because it had a rare antimicrobial resistance pattern and a highly unusual plasmid profile; study of stored isolates showed it had caused clusters of salmonellosis during the previous ten months that may have been related to the same plant, suggesting that the strain had persisted in the plant and repeatedly contaminated milk after pasteurization.

Adolescent↗
PubMed1987

Three-dimensional structure of potato carboxypeptidase inhibitor in solution. A study using nuclear magnetic resonance, distance geometry, and restrained molecular dynamics.

The solution conformation of potato carboxypeptidase inhibitor (CPI) has been investigated by 1H NMR spectroscopy. The spectrum is assigned in a sequential manner by using two-dimensional NMR techniques to identify through-bond and through-space (less than 5 A) connectivities. A set of 309 approximate interproton distance restraints is derived from the two-dimensional nuclear Overhauser enhancement spectra and used as the basis of a three-dimensional structure determination by a combination of metric matrix distance geometry and restrained molecular dynamics calculations. A total of 11 converged distance geometry structures were computed and refined by using restrained molecular dynamics. The average atomic root mean square (rms) difference between the final 11 structures and the mean structure obtained by averaging their coordinates is 1.4 +/- 0.3 A for residues 2-39 and 0.9 +/- 0.2 A for residues 5-37. The corresponding values for all atoms are 1.9 +/- 0.3 and 1.4 +/- 0.2 A, respectively. The larger values for residues 2-38 relative to those for residues 5-37 arise from the fact that the positions of the N- (residues 1-4) and C- (residues 38-39) terminal tails are rather poorly determined, whereas those of the core of the protein (residues 5-37) are well determined by the experimental interproton distance data. The computed structures are very close to the X-ray structure of CPI in its complex with carboxypeptidase, and the backbone atomic rms difference between the mean of the computed structures and the X-ray structure is only 1.2 A. Nevertheless, there are some real differences present which are evidenced by significant deviations between the experimental upper interproton distance limits and the corresponding interproton distances derived from the X-ray structure. These principally occur in two regions, residues 18-20 and residues 28-30, the latter comprising part of the region of secondary contacts between CPI and carboxypeptidase in the X-ray structure.

Carboxypeptidases↗
PubMed1987

Subcapsular hematoma of the liver in infants of very low birth weight.

Between January 1982 and May 1986 a large subcapsular hemorrhage of the liver (SHL) was diagnosed in six infants who weighed 1000 g or less at birth at Royal Alexandria Hospitals, Edmonton. The diagnosis of a ruptured SHL was made between 4 and 18 days of life by means of clinical and sonographic findings in four of the infants; an intact SHL was diagnosed at autopsy in the other two. None of the cases was associated with parenchymal rupture of the liver. Thrombocytopenia was present in five of the six infants and in all four infants with hemoperitoneum. Other possibly relevant antecedent events included mechanical ventilation (in all six), administration of indomethacin (in all six), hypoxia (in five), bilateral pneumothorax necessitating repeated pleural drainage (in three), external cardiac massage (in three) and septicemia (in two). Two of the three infants who underwent surgery survived the operation but later died of unrelated events. One infant who was managed conservatively also survived. A large SHL should be considered in all infants of very low birth weight with unexplained hypovolemia or anemia.

Diseases in Twins↗